Intracellular crosstalk mediated by calcium ions (Ca2+) is fundamentally important for understanding regulation of cellular function. Cellular Ca2+ fluxes and mitochondrial Ca2+ dynamics, influence the activity of mitochondrial enzymes involved in energy metabolism and cellular redox. These changes influence post-translational modification of proteins in mitochondria, the cytoplasm and the nucleus, which control cell functions such as energy metabolism and transcription. We hypothesize that Ca2+ signaling by mitochondria in photoreceptors is critical for their function and survival. The study proposed here will define how photoreceptor activity is regulated by mitochondrial Ca2+ to meet the specialized demands of this unique sensory neuron. Using genetically encoded Ca2+ indicators and in vivo imaging, we have documented large Ca2+ fluctuations in the cell bodies and mitochondria of zebrafish cone photoreceptors. We also developed methods for manipulating Ca2+ in cell bodies and mitochondria and for detecting protein modifications and cellular redox changes. We will use these methods to determine how Ca2+ fluxes within photoreceptors are processed by mitochondria. We will study how mitochondria regulate Ca2+ in photoreceptor cell bodies and the role of the mitochondrial Ca2+ uniporter (Aim 1). We also will determine how Ca2+ controls the cytoplasmic redox potential and acylation of proteins (Aim 2).